15-74820742-A-G

Position:

• chr15-74820742-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021819.3(LMAN1L):​c.882A>G​(p.Lys294=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 1,613,098 control chromosomes in the GnomAD database, including 14,217 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (3586 hom., cov: 32)
  • Exomes 𝑓: 0.075 (10631 hom.)
• Consequence: LMAN1L NM_021819.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

Genes affected

LMAN1L (HGNC:6632): (lectin, mannose binding 1 like) This gene encodes a mannose-binding type 1 transmembrane protein that contains an N-terminal lectin-like carbohydrate recognition domain. The encoded protein is similar in structure to lectins found in leguminous plants. This lectin is thought to transport newly synthesized glycoproteins from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=0.074 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMAN1L	NM_021819.3	c.882A>G	p.Lys294=	synonymous_variant	8/14	ENST00000309664.10	NP_068591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMAN1L	ENST00000309664.10	c.882A>G	p.Lys294=	synonymous_variant	8/14	1	NM_021819.3	ENSP00000310431	P1
LMAN1L	ENST00000379709.7	c.846A>G	p.Lys282=	synonymous_variant	7/13	1		ENSP00000369031
LMAN1L	ENST00000565585.5	n.1276A>G		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24092 AN: 151912 Hom.: 3569 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.0791

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.129

GnomAD3 exomes AF: 0.132 AC: 33083 AN: 250460 Hom.: 4284 AF XY: 0.134 AC XY: 18073 AN XY: 135366

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.0648

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.337

Gnomad FIN exome AF: 0.0735

Gnomad NFE exome AF: 0.0372

Gnomad OTH exome AF: 0.0994

GnomAD4 exome AF: 0.0752 AC: 109907 AN: 1461068 Hom.: 10631 Cov.: 32 AF XY: 0.0814 AC XY: 59186 AN XY: 726782

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.0659

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.0689

Gnomad4 NFE exome AF: 0.0371

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.159 AC: 24155 AN: 152030 Hom.: 3586 Cov.: 32 AF XY: 0.164 AC XY: 12154 AN XY: 74334

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.0791

Gnomad4 NFE AF: 0.0382

Gnomad4 OTH AF: 0.135

Alfa AF: 0.0822 Hom.: 857

Bravo AF: 0.167

Asia WGS AF: 0.339 AC: 1175 AN: 3478

EpiCase AF: 0.0368

EpiControl AF: 0.0426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1531163; hg19: chr15-75113083; COSMIC: COSV59001100; COSMIC: COSV59001100;